This proposal outlines new synthetic techniques and advances made under CA 16432 which will be applied to cytotoxic and antineoplastic natural products. The method developed in the Laboratory for the unsymmetrical coupling of aryls will be applied to the antileukemics steganancin and steganangin, which show activity in vivo against P-388 leukemia in mice in vitro against cells of human carcinoma of the nasopharynx (KB). Synthetic studies on the alpha-methylene gamma-butyrolactones eriolanin and eriolangin, which show similar activity, will be continued. New methods for constructing the pseudoguaianolide skeleton applicable to the synthesis of multiradiatin and fastigilin c, which display in vitro P-388 activity and in vivo activity in the PS screen. New reactions with sulfur reagents will be explored as they apply to the synthesis of guaianolides.